Abstract: Genome sequences of all important model organisms are now available, thanks to technological advances in high throughput DNA sequencing. The next step in understanding biology and disease is to identify protein interactome. However, unlike the genome, protein interactome is dynamic and contains weakly associated components, which hit the blind spots of current technologies. Hence, toward construction of a complete human interactome, I propose to develop a new principle-based technology for labeling and identifying both strongly and weakly interacting proteins. This new technology will be demonstrated in deorphanization of GPCRs, identification of substrates of ubiquitin E3 ligases, and identification of chaperon networks. Public Health Relevance: Protein-protein interaction networks underlie most cellular processes. To understand biology and disease and to identify new therapeutic targets, the proposed new technology aims to search, analyze and visualize protein-protein interaction networks.